Helium-induced preconditioning in young and old rat heart: impact of mitochondrial Ca(2+) -sensitive potassium channel activation.
BACKGROUND
The noble gas helium induces cardiac preconditioning. Whether activation of mitochondrial K(+) channels is involved in helium preconditioning (He-PC) is unknown. The authors investigated whether He-PC (1) is mediated by activation of Ca(2+) -sensitive potassium channels, (2) results in mitochondrial uncoupling, and (3) is age dependent.


METHODS
Anesthetized Wistar rats were randomly assigned to six groups (n = 10 each). Young (2-3 months) control (Con) and aged (22-24 months) control animals (Age Con) were not treated further. Preconditioning groups (He-PC and Age He-PC) inhaled 70% helium for 3 x 5 min. The Ca(2+) -sensitive potassium channel blocker iberiotoxin was administered in young animals, with and without helium (He-PC+Ibtx and Ibtx). Animals underwent 25 min of regional myocardial ischemia and 120 min of reperfusion. In additional experiments, cardiac mitochondria were isolated, and the respiratory control index was calculated (state 3/state 4).


RESULTS
Helium reduced infarct size in young rats from 61 +/- 7% to 36 +/- 14% (P < 0.05 vs. Con). Infarct size reduction was abolished by iberiotoxin (60 +/- 11%; P < 0.05 vs. He-PC), whereas iberiotoxin alone had no effect (59 +/- 8%; not significant vs. Con). In aged animals, helium had no effect on infarct size (Age Con: 59 +/- 7% vs. Age He-PC: 58 +/- 8%; not significant). Helium reduced respiratory control index in young animals (2.76 +/- 0.05 to 2.43 +/- 0.15; P < 0.05) but not in aged animals (Age Con: 2.87 +/- 0.17 vs. Age He-PC: 2.87 +/- 0.07; not significant). Iberiotoxin abrogated the helium effect on respiratory control index (2.73 +/- 0.15; P < 0.05 vs. He-PC) but had no effect itself on mitochondrial respiration (2.75 +/- 0.05; not significant vs. Con).


CONCLUSIONS
Helium causes mitochondrial uncoupling and induces preconditioning in young rats via Ca(2+) -sensitive potassium channel activation. However, these effects are lost in aged rats.
Heinen
Andre
A
Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Huhn
Ragnar
R
Smeele
Kirsten M A
KM
Zuurbier
Coert J
CJ
Schlack
Wolfgang
W
Preckel
Benedikt
B
Weber
Nina C
NC
Hollmann
Markus W
MW
D000367:Age Factors; D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D006371:Helium / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D024681:Potassium Channels, Calcium-Activated; D006371:Helium